CHR15 is a human-specific fusion gene that functions as a dominant negative regulator of the α7 nicotinic acetylcholine receptor (α7 nAChR) 1. The gene produces the dupα7 protein, which assembles with native α7 subunits to form heteromeric receptors with reduced functional activity compared to homopentameric α7 receptors 2. CHR15/α7 nAChR functions as a hypomorphic receptor with mitigated Ca2+ influx and prolonged channel closed states, shifting Ca2+ dynamics from extracellular to endoplasmic reticulum sources 3. This altered Ca2+ signaling activates the small GTPase Rac1, reorganizing the actin cytoskeleton and affecting cellular adhesion, motility, and phagocytosis 3. The gene is highly expressed in human leukocytes and plays important roles in inflammatory regulation 4. CHR15 has complex disease associations, showing protective effects in renal fibrosis by inhibiting TGF-β1/Smad2/3 signaling pathways 5, while being associated with more severe osteoarthritis and amplified pain behaviors 6. The absence of CHR15 in animal models may contribute to the translational gap in α7 nAChR drug development, as therapeutic effects observed in preclinical studies often fail in human trials 7.